{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:26:38Z","timestamp":1781533598317,"version":"3.54.5"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"publisher","award":["R01HS024057"],"award-info":[{"award-number":["R01HS024057"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate response to anti\u2010calcitonin gene\u2013related peptide (CGRP) migraine preventives in a real\u2010world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erenumab\u2010aooeb, fremanezumab\u2010vrfm, and galcanezumab\u2010gnlm target CGRP or its receptor; however, many patients are non\u2010responsive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti\u2010CGRP migraine preventive between May 2018 and May 2021. Screening of 558 patients identified 289 with data at baseline and first follow\u2010up visits; data were available for 161 patients at a second follow\u2010up visit. The primary outcome was migraine days per month (MDM). In 198 genotyped patients, we evaluated associations between responders (i.e., patients with \u226550% reduction in MDM at follow\u2010up) and genes involved in CGRP signaling or pharmacological response, and genetic and polygenic risk scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median time to first follow\u2010up was 4.4 (0.9\u201322) months after preventive start. At the second follow\u2010up, 5.7 (0.9\u201313) months later, 145 patients had continued on the same preventive. Preventives had strong, persistent effects in reducing MDM in responders (follow\u2010up 1:\n                      <jats:italic>\u03b7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.26, follow\u2010up 2:\n                      <jats:italic>\u03b7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.22). At the first but not second follow\u2010up: galcanezumab had a larger effect than erenumab, while no difference was seen at either follow\u2010up between galcanezumab and fremanezumab or fremanezumab and erenumab. The decrease in MDM at follow\u2010up was generally proportional to baseline MDM, larger in females, and increased with months on medication. At the first follow\u2010up only, patients with prior hospitalization for migraine or who had not responded to more preventive regimens had a smaller decrease in MDM. Reasons for stopping or switching a preventive varied between medications and were often related to cost and insurance coverage. At both follow\u2010ups, patient tolerance (1: 92.2% [262\/284]; 2: 95.2% [141\/145]) and continued use (1: 77.5% [224\/289]; 2: 80.6% [116\/145]) were high and similar across preventives. Response consistency (always non\u2010responders: 31.7% [46\/145]; always responders: 56.5% [82\/145], and one\u2010time only responders: 11.7% [17\/145]) was also similar across preventives. Non\u2010responder status had nominally significant associations with\n                      <jats:italic>rs12615320\u2010<\/jats:italic>\n                      G in\n                      <jats:italic>RAMP1<\/jats:italic>\n                      (odds ratio [95% confidence interval]: 4.7 [1.5, 14.7]), and\n                      <jats:italic>rs4680\u2010<\/jats:italic>\n                      A in\n                      <jats:italic>COMT<\/jats:italic>\n                      (0.6[0.4, 0.9]). Non\u2010responders had a lower mean genetic risk score than responders (1.0 vs. 1.1;\n                      <jats:italic>t<\/jats:italic>\n                      (\n                      <jats:italic>df<\/jats:italic>\n                      )\u2009=\u2009\u22121.75(174.84),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041), and the fraction of responders increased with genetic and polygenic risk score percentile.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this real\u2010world setting, anti\u2010CGRP preventives reduced MDM persistently and had similar and large effect sizes on MDM reduction; however, clinical and genetic factors influenced response.<\/jats:p>\n                  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